Primary and acquired resistance to anti-epidermal growth factor receptor (EGFR) drugs are clinically relevant problems in patients with metastatic colorectal carcinoma. A complex network of molecular alterations is involved in this phenomenon. Bertotti et al. report the development of serially transplantable groups of tumor xenografts in immune-deficient mice from patient-derived, genetically characterized metastatic colorectal carcinoma samples. These experimental models ("xenopatients") might represent a novel approach to discover and characterize the mechanisms of resistance to anti-EGFR therapy and other molecularly targeted therapies in metastatic colorectal carcinoma. In this respect, Bertotti et al. were able to identify HER2 gene amplification as one such mechanism of resistance to anti-EGFR therapy.
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